Ca2+-activated transbilayer movement of plasma membrane phospholipids in Leishmania donovani during ionomycin or thapsigargin stimulation

Adrien Weingärtner; Marcos Gonzaga dos Santos; Björn Drobot; Thomas Günther-Pomorski

doi:10.1016/j.molbiopara.2011.05.006

Ca²⁺-activated transbilayer movement of plasma membrane phospholipids in Leishmania donovani during ionomycin or thapsigargin stimulation

Adrien Weingärtner, Marcos Gonzaga dos Santos, Björn Drobot, Thomas Günther-Pomorski

2 Citations (Scopus)

Abstract

The protozoan parasite Leishmania causes serious infections in humans all over the world. After being inoculated into the skin through the bite of an infected sandfly, Leishmania promastigotes must gain entry into macrophages to initiate a successful infection. Specific, surface exposed phospholipids have been implicated in Leishmania-macrophage interaction but the mechanisms controlling and regulating the plasma membrane lipid distribution remains to be elucidated. Here, we provide evidence for Ca²⁺-induced phospholipid scrambling in the plasma membrane of Leishmania donovani. Stimulation of parasites with ionomycin increases intracellular Ca²⁺ levels and triggers exposure of phosphatidylethanolamine at the cell surface. We found that increasing intracellular Ca²⁺ levels with ionomycin or thapsigargin induces rapid transbilayer movement of NBD-labelled phospholipids in the parasite plasma membrane that is bidirectional, independent of cellular ATP and not specific to the polar lipid head group. The findings suggest the presence of a Ca²⁺-dependent lipid scramblase activity in Leishmania parasites. Our studies further show that lipid scrambling is not activated by rapid exposure of promastigotes to higher physiological temperature that increases intracellular Ca²⁺ levels.

Original language	English
Journal	Molecular and Biochemical Parasitology
Volume	179
Issue number	2
Pages (from-to)	59-68
Number of pages	10
ISSN	0166-6851
DOIs	https://doi.org/10.1016/j.molbiopara.2011.05.006
Publication status	Published - Oct 2011

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Ca²⁺-activated transbilayer movement of plasma membrane phospholipids in Leishmania donovani during ionomycin or thapsigargin stimulation. / Weingärtner, Adrien; Santos, Marcos Gonzaga dos; Drobot, Björn et al.
In: Molecular and Biochemical Parasitology, Vol. 179, No. 2, 10.2011, p. 59-68.

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title = "Ca2+-activated transbilayer movement of plasma membrane phospholipids in Leishmania donovani during ionomycin or thapsigargin stimulation",

abstract = "The protozoan parasite Leishmania causes serious infections in humans all over the world. After being inoculated into the skin through the bite of an infected sandfly, Leishmania promastigotes must gain entry into macrophages to initiate a successful infection. Specific, surface exposed phospholipids have been implicated in Leishmania-macrophage interaction but the mechanisms controlling and regulating the plasma membrane lipid distribution remains to be elucidated. Here, we provide evidence for Ca2+-induced phospholipid scrambling in the plasma membrane of Leishmania donovani. Stimulation of parasites with ionomycin increases intracellular Ca2+ levels and triggers exposure of phosphatidylethanolamine at the cell surface. We found that increasing intracellular Ca2+ levels with ionomycin or thapsigargin induces rapid transbilayer movement of NBD-labelled phospholipids in the parasite plasma membrane that is bidirectional, independent of cellular ATP and not specific to the polar lipid head group. The findings suggest the presence of a Ca2+-dependent lipid scramblase activity in Leishmania parasites. Our studies further show that lipid scrambling is not activated by rapid exposure of promastigotes to higher physiological temperature that increases intracellular Ca2+ levels.",

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AU - Santos, Marcos Gonzaga dos

AU - Drobot, Björn

AU - Günther-Pomorski, Thomas

PY - 2011/10

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N2 - The protozoan parasite Leishmania causes serious infections in humans all over the world. After being inoculated into the skin through the bite of an infected sandfly, Leishmania promastigotes must gain entry into macrophages to initiate a successful infection. Specific, surface exposed phospholipids have been implicated in Leishmania-macrophage interaction but the mechanisms controlling and regulating the plasma membrane lipid distribution remains to be elucidated. Here, we provide evidence for Ca2+-induced phospholipid scrambling in the plasma membrane of Leishmania donovani. Stimulation of parasites with ionomycin increases intracellular Ca2+ levels and triggers exposure of phosphatidylethanolamine at the cell surface. We found that increasing intracellular Ca2+ levels with ionomycin or thapsigargin induces rapid transbilayer movement of NBD-labelled phospholipids in the parasite plasma membrane that is bidirectional, independent of cellular ATP and not specific to the polar lipid head group. The findings suggest the presence of a Ca2+-dependent lipid scramblase activity in Leishmania parasites. Our studies further show that lipid scrambling is not activated by rapid exposure of promastigotes to higher physiological temperature that increases intracellular Ca2+ levels.

AB - The protozoan parasite Leishmania causes serious infections in humans all over the world. After being inoculated into the skin through the bite of an infected sandfly, Leishmania promastigotes must gain entry into macrophages to initiate a successful infection. Specific, surface exposed phospholipids have been implicated in Leishmania-macrophage interaction but the mechanisms controlling and regulating the plasma membrane lipid distribution remains to be elucidated. Here, we provide evidence for Ca2+-induced phospholipid scrambling in the plasma membrane of Leishmania donovani. Stimulation of parasites with ionomycin increases intracellular Ca2+ levels and triggers exposure of phosphatidylethanolamine at the cell surface. We found that increasing intracellular Ca2+ levels with ionomycin or thapsigargin induces rapid transbilayer movement of NBD-labelled phospholipids in the parasite plasma membrane that is bidirectional, independent of cellular ATP and not specific to the polar lipid head group. The findings suggest the presence of a Ca2+-dependent lipid scramblase activity in Leishmania parasites. Our studies further show that lipid scrambling is not activated by rapid exposure of promastigotes to higher physiological temperature that increases intracellular Ca2+ levels.

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DO - 10.1016/j.molbiopara.2011.05.006

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SN - 0166-6851

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EP - 68

JO - Molecular and Biochemical Parasitology

JF - Molecular and Biochemical Parasitology

IS - 2

ER -

Ca2+-activated transbilayer movement of plasma membrane phospholipids in Leishmania donovani during ionomycin or thapsigargin stimulation

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Ca²⁺-activated transbilayer movement of plasma membrane phospholipids in Leishmania donovani during ionomycin or thapsigargin stimulation